Effects of combination therapy with an angiotensin converting enzyme inhibitor and thiazide diuretic on insulin action in essential hypertension

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ObjectiveTo determine whether combination of an angiotensin converting enzyme inhibitor with a high dose of thiazide diuretic avoids adverse metabolic consequences of thiazide diuretics.DesignDouble-blind randomized crossover study of two 12-week treatment periods with captopril (up to 100 mg/day) either alone or in combination with 5 mg bendrofluazide given after a 6-week placebo run-in period. Treatment periods were separated by a 6-week placebo washout period.SettingOutpatient clinics in greater Belfast.PatientsFifteen white non-diabetic essential hypertensives (seven male) aged < 65 years recruited from general practices in greater Belfast.Main outcome measuresSystolic and diastolic blood pressures and peripheral and hepatic insulin action.ResultsTwo patients failed to complete the study. Blood pressure was lowered (139/89 ± 18/7 mmHg combination versus 160/97 ± 21/7 mmHg captopril; P < 0.001). Fasting insulin level was raised (7.9 ± 3.6 mU/l combination versus 6.2 ± 3.2 mU/l baseline; P < 0.001). There were no differences between treatments for glucose, urate, cholesterol and triglyceride levels. Serum potassium level was lowered (3.8 ± 0.4 μmol/l combination versus 4.2 ± 0.4 μmol/l captopril, P < 0.05). Postabsorptive endogenous glucose production was raised (10.8 ± 1.7 μmol/kg per min combination versus 10.0 ± 1.5 μmol/kg per min captopril; P < 0.01) and was greater than baseline (9.7 ± 2.1 μmol/kg per min, P < 0.05). Suppression of glucose production by insulin was similar with both treatments. Exogenous glucose infusion rates required to maintain euglycaemia did not differ (32.4 ± 7.6 μmol/kg per min captopril, 32.7 ± 6.2 μmol/kg per min combination, 31.5 ± 7.2 μmol/kg per min baseline).ConclusionsCombination therapy increased glucose production (compared with captopril alone), indicating hepatic insulin resistance. It cannot be assumed that combined preparations with angiotensin converting enzyme inhibitors will ameliorate adverse effects of high doses of thiazide diuretics on insulin action.

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